Osteoarthritis (OA) is the most common form of arthritis affecting millions of Americans; there is a paucity of effective treatments. Inflammation is critical factor affecting pain in OA and also causing structural deterioration in the joint. Dietary factors can modify inflammation and it is the goal of this project to test evidence regarding specific dietary factors that can affect inflammation and for which there is evidence linking that dietary factor to OA. Among factors to be studied include specific fatty acids whose effects on inflammation differ. Among those to be examined are Omega-3 fatty acids which have anti-inflammatory effects and saturated fatty acids, which can enhance inflammation and have been shown in animal studies to accelerate the development of OA. LDL cholesterol has also been linked to OA in ex vivo human and animal studies and we will also examine its with OA. Circulating fatty acid profiles and LDL have not been assessed for their effects on OA in longitudinal human studies. For dietary fiber, numerous studies have pointed to a protective effect on diabetes, heart disease and even mortality. Dietary fiber may reduce systemic inflammation and reduce weight and in recent work from 2 studies, we have found preliminary evidence that dietary fiber intake reduces risk of knee OA. We want to pursue this finding with more definitive work. The overall goal of the proposed project is to comprehensively and longitudinally evaluate whether circulating fatty acid profiles, LDL and fiber modify the risk of symptomatic knee OA. What ties together these factors is that they are all factors affecting inflammation and all modifiable through dietary alterations, something that is inexpensive and greatly desired by patients. To ask these questions we shall take advantage of data from the MOST cohort study, a longitudinal study of 3,026 persons with or at risk of knee OA evaluated for OA serially over 60 months. Baseline biological samples obtained after an overnight fast will allow us to test the associations of fatty acids, LDL and alkylresorcinol, a biomarker of fiber intake, with incident OA. For each of the dietary measures we shall study the incidence of symptomatic OA which is the phenotype of OA with clinical and public health importance consisting of the combination of pain and radiographic OA. There is already preliminary bench science data supporting the association of the dietary factors we are studying. Positive findings from this project will provide sufficient data to warrant clinical trials testing specific dietary treatments for OA and offering the realistic possibility that dietary modifications may enter the therapeutic armamentarium for OA.